%0 Journal Article
%T Neuroinflammation and Copper in Alzheimer¡¯s Disease
%A Xin Yi Choo
%A Lobna Alukaidey
%A Anthony R. White
%A Alexandra Grubman
%J International Journal of Alzheimer's Disease
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/145345
%X Inflammation is the innate immune response to infection or tissue damage. Initiation of proinflammatory cascades in the central nervous system (CNS) occurs through recognition of danger associated molecular patterns by cognate immune receptors expressed on inflammatory cells and leads to rapid responses to remove the danger stimulus. The presence of activated microglia and astrocytes in the vicinity of amyloid plaques in the brains of Alzheimer¡¯s disease (AD) patients and mouse models implicates inflammation as a contributor to AD pathogenesis. Activated microglia play a critical role in amyloid clearance, but chronic deregulation of CNS inflammatory pathways results in secretion of neurotoxic mediators that ultimately contribute to neurodegeneration in AD. Copper (Cu) homeostasis is profoundly affected in AD, and accumulated extracellular Cu drives A¦Â aggregation, while intracellular Cu deficiency limits bioavailable Cu required for CNS functions. This review presents an overview of inflammatory events that occur in AD in response to A¦Â and highlights recent advances on the role of Cu in modulation of beneficial and detrimental inflammatory responses in AD. 1. Inflammation Inflammation is a protective response rapidly triggered by innate immune cells in the event of tissue injury, as well as endogenous or exogenous insults (reviewed in [1]). The process is highly complicated, involving the complex interplay of cells and mediators. In brief, acute inflammatory responses involve vasodilation to increase blood flow combined with alterations in microvascular structure to allow exit of circulating leukocytes and plasma proteins, followed by accumulation and activation of leukocytes at the site of injury, where leukocyte extravasation is largely facilitated by cytokines including tumour necrosis factor (TNF) and interleukin-1 (IL-1) [1]. In addition, activated innate immune cells at site of injury remove cellular debris and/or pathogens via phagocytosis with concomitant cytokine production to facilitate the initiation of adaptive responses [1]. Due to the variability in the nature, severity, and site of injuries, resolution of inflammatory processes, where all injury and insults become resolved with little tissue damage, is not always possible. For severe tissue damage where regeneration is insufficient, healing with fibrosis may occur instead. The third possible outcome is progression from acute to chronic inflammation. This occurs when danger signals persist and inflammation cannot be resolved. Notably, a wide range of diseases, including asthma [2],
%U http://www.hindawi.com/journals/ijad/2013/145345/